1. ¹Department of Pathology, School of Medicine, Tokushima University, Tokushima
2. ²Department of Neurosurgery, School of Medicine, Tokushima University, Tokushima
3. ³Department of Pharmacology, School of Dentistry, Tokushima University, Tokushima
4. ⁴Department of Neurosurgery, Toranomon Hospital, Tokyo, Japan
5. ⁵Department of Pathology and Laboratory Medicine, Veterans General Hospital-Taipei and National Yung-Ming University, Taipei, Taiwan

Correspondence: Toshiaki Sano, M.D., Ph.D., Department of Pathology, University of Tokushima School of Medicine, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan; e-mail: sano@basic.med.tokushima-u.ac.jp; fax: 81-88-633-9423.

Accepted 3 September 2002.

Abstract

E-cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. In a number of cancers, abnormal and reduced expression of E-cadherin/catenin complex is associated with tumor invasion and metastasis. Prolactinomas show frequent invasion on the surrounding structures, despite their histologically benign nature. Furthermore, gender-based differences in endocrine and surgical findings are found in patients with prolactinoma. To understand biological factors governing prolactinoma behavior, this study analyzed the expression of E-cadherin; -, -, and -catenins; p120; and cell proliferation marker MIB-1 labeling index in 13 invasive tumors (9 in men, 4 in women), 26 noninvasive tumors (4 in men, 22 in women), and 8 normal anterior pituitaries by immunohistochemistry. Immunostaining of E-cadherin; -, -, and -catenins; and p120 showed a membranous pattern of reactivity and generally stronger in normal pituitaries than in prolactinomas. Expression of E-cadherin and -catenin was significantly lower in invasive than in noninvasive prolactinomas (P <.002 and P <.005, respectively), and reduced expression of E-cadherin and -catenin was more frequent in invasive than in noninvasive prolactinomas (P <.001 and P <.05, respectively); in contrast, -catenin expression showed higher in invasive than in noninvasive prolactinomas (P <.05). Expression of E-cadherin was significantly lower in macroprolactinomas than in microprolactinomas (P <.01), and decreased expression of E-cadherin and -catenin predicted high MIB-1 expression (P <.05). Moreover, the expression of E-cadherin and -catenin was significantly lower in macroprolactinomas in men than in those in women (P <.01 and P <.02, respectively). No statistical correlations were observed between expression of -catenin, p120, and clinicopathologic features. In conclusion, the reduction of E-cadherin and -catenin expression was related to invasiveness and proliferative status of prolactinomas and correlated with the more aggressive behavior of prolactinomas in men compared with in women.